Increased expression of angiogenin in gastric carcinoma in correlation with tumor angiogenesis and proliferation

AIM: To investigate the implication of angiogenin (ANG) in the neovascularizaton and growth of human gastric carcinoma (HGC). METHODS: ANG mRNA expression in HGC specimens obtained by surgical resection from patients with HGC were examined by RT-PCR. ANG, Ki-67, VEGF protein expression and microvessel density (MVD) in HGC specimens were detected by immunohistochemistry. RESULTS: RT-PCR showed significantly higher ANG mRNA expression (0.482±0.094) in HGC tissues than in the surrounding nontumorous tissues (0.276±0.019, P=0.03). MVD within tumorous tissues increased significantly with ANG mRNA expression (r=0.380,P=0.001) and ANG protein expression (P<0.01). The ANG expression levels of cancer tissues were positively correlated with VEGF (P<0.01) and the proliferation index of cancer cells (P<0.01). CONCLUSION: ANG is one of the neovascularization factors of HGC. ANG may work in coordination with VEGF, and promote the proliferation of HGC cells.     

胃癌组织碱性成纤维细胞生长因子表达及对血管新生和肿瘤进展的影响

目的　探讨碱性成纤维细胞生长因子 (bFGF)在胃癌组织中表达及其对血管新生和肿瘤生物学行为的影响。方法　应用免疫组化SP法检测 74例胃癌 ,17例癌旁组织bFGF表达及间质微血管密度 (MVD)。结果　胃癌组织中肿瘤细胞、间质新生血管高度表达bFGF。癌组织bFGF表达(77.0 3% )明显高于癌旁组织 (2 9.4 1% ,P <0 .0 1)。癌旁胃黏膜及伴有肠上皮化生的胃黏膜表达bFGF较弱。bFGF高表达组的平均MVD值 (79.3± 11.2 )明显高于bFGF低表达组 (71.2± 11.9,P <0 .0 5 )。此外bFGF表达程度与胃癌淋巴结转移和癌浸润深度密切相关。结论　bFGF可促进肿瘤间质微血管生成 ,加速肿瘤浸润和转移。     

H pylori status and angiogenesis factors in human gastric carcinoma

INTRODUCTION H pylori infection is a well-known risk factor for the development of pre-neoplastic and neoplastic gastric mucosal alterations[1,2]. An increase in proliferative activity of gastric epithelial cells without a corresponding increase in apopto…     

EB病毒感染与血管生成在胃癌组织芯片中的关系

目的:探讨EB病毒(Epstein-Barr virus,EBV)感染相关胃癌的构成比,其淋巴结转移癌的感染状况、临床病理特征及与血管生成的关系.方法:用原位杂交法检测胃癌组织中EBV编码的小RNA(EBERs),分析EB病毒相关胃癌的病理形态、患者年龄、性别、淋巴结转移状况等临床特征;用免疫组织化学EnVision法检测血管生成(即血管内皮生长因子(vascular endothelial growth factor,VEGF)蛋白的表达水平,分析EBV和血管生成在胃癌的表达与患者淋巴结转移状态、Lauren's分型等的关系及其相互关系.结果:486例胃癌患者中检测出感染EB病毒者(n=18,3.7%).该病毒位于肿瘤细胞核内;14例EB病毒相关胃癌患者中(77.8%)伴淋巴结转移癌,其中所有癌细胞均表达EBERs;与非EB病毒感染胃癌相比,EB病毒相关胃癌分化程度低(P<0.05),而临床TNM分期无明显差别(P>0.05);血管生成在胃癌组织中的表达率(28.2%,137/486);血管生成与患者淋巴结转移状态,TNM分期相关(P<0.05);同时,血管生成与EBV感染胃癌二者之间呈正相关(r=0.08...     

Transcription factor Sp1 expression in gastric cancer and its relationship to long-term prognosis

AIM: To explore the expression of Spl in gastric carcinoma as well as its association with other clinicopathologic features, and to evaluate the role of Spl as a prognostic indicator of gastric carcinoma.METHODS: By using immunohistochemistry, we examined the Sp1 expression patterns in 65 cases of human gastric cancer, and 40 normal gastric mucosa specimens. Simultaneously, the correlation between Sp1 expression and clinical outcome or clinicopathologic features was investigated.RESULTS: The percentage of Spl expression was 12.5% (5/40) in normal gastric mucosa, and the Sp1 protein was mainly expressed in the nuclei of cells located in the mucous neck region. In sharp contrast, strong Sp1 expression was detected in tumor cells, whereas no or faint Sp1 staining was detected in stromal cells and normal glandular cells surrounding the tumors. The expression rate of Sp1 in gastric cancer lesions was 53.85% (35/65). The medium survival duration in patients who had a tumor with negative, weak and strong Sp1 expressions was 1700, 1560 and 1026d, respectively (P&lt;0.05). Sp1 protein expression was closely related to the depth of tumor infiltration (x^2=13.223, P&lt;0.01) and TNM stage (x^2=11.009, P&lt;0.05), but had no relationship with the number of lymph nodes and Lauren‘s classification (P&gt;0.05). Cox regression model for multivariate analysis revealed that high Spl expression (P&lt;0.05) and advanced stage (P&lt;0.01) were independent predictors of poor survival.CONCLUSION: Normal and malignant gastric tissues have unique Sp1 expression patterns. Spl might serve as an independent prognostic factor, by influencing the tumor infiltration and progression.     

人胃癌组织MCP-1表达与肿瘤血管生成的关系

目的研究人胃癌组织中单核细胞趋化蛋白-1(MCP-1)和血管内皮生长因子(VEGF)的表达及其与微血管计数的关系.方法用免疫组化方法对80例胃癌手术标本组织中MCP-1与肿瘤组织中主要的血管生成因子VEGF的表达以及与肿瘤血管计数之间的关系进行探讨.同时对MCP-1表达和血管计数与临床病理特征之间的关系进行探讨.结果(1) 血管计数随组织学分级程度的增高而增加;胃癌组织中MCP-1阳性率随组织学分级程度的增高而增高,但只有低分化组与高分化组比较差异有统计学意义P<0.01);(2)胃癌组织中血管计数及MCP-1表达阳性率随肿瘤浸润深度的增加而增高;(3)淋巴结转移阳性与阴性胃癌组织比较,血管计数显著升高, MCP-1表达阳性率也有相似的结果;(4)VEGF表达阳性组织与阴性组织比较,血管计数显著升高,且胃癌细胞中VEGF表达阳性者MCP-1阳性率较高;(5)MCP-1主要表达于肿瘤细胞,MCP-1阳性组微血管计数显著高于MCP-1阴性组.MCP-1阳性组胃癌细胞VEGF表达较高.结论MCP-1蛋白主要表达于胃癌组织的肿瘤细胞中,它可促进VEGF的表达,VEGF的表达又促进肿瘤新生血管生成;胃癌组织中MCP-1表达和微血管计数与肿瘤的组织学分级、浸润深度、淋巴结转移存在相关关系.MCP-1可能通过增加肿瘤相关巨噬细胞(TAM)的浸润刺激肿瘤血管生成.     

Assessment of the proliferation index in gastric carcinomas with the monoclonal antibody MIB 1

Our study aimed to reveal whether the proliferation index of tumor cells, calculated with the monoclonal antibody (mAb) MIB1, is of prognostic relevance in patients with a gastric carcinoma and shows any correlation to well-known clinicopathological factors (TNM categories, stage, grade, Laurén type). We examined formalin-fixed, paraffin-embedded tissue blocks of samples from 94 patients, who underwent surgery for an adenocarcinoma of the stomach between 1988 and 1991. Specimens were immunohistochemically stained using the mAb MIB1 in combination with the alkaline-phosphatase/anti-(alkaline phosphatase) technique. The proliferation index (PI) was estimated in various areas of interest (tumor center and periphery and in lymph node metastases of compartments I and II), by always counting 200 tumor cells in three different high-power fields per specimen, and calculated as the percentage of MIB1-positive tumor cell nuclei relative to all tumor cell nuclei in the area examined. The total PI in the primary tumor was 47.2% and slightly higher in the center (49.1%) compared to the periphery (44.7%). Surprisingly in lymph node metastases the PI was lower than in the primary tumor (compartment I: 39.5%, compartment II: 33.6%). Tumors with distant metastases revealed a higher proliferative activity (55.1%) than tumors without (44.3%). The PI increased significantly from well to poorly differentiated carcinomas (P < 0.01), whereas the intestinal Laurén type showed a lower PI than the diffuse type. No difference in survival was found between patients with a median PI or less and those with a PI above the median (47.2%). Our results show that the proliferation index in gastric carcinomas has no prognostic relevance and therefore is of low clinical value. Received: 11 July 1997 / Accepted: 30 September 1997     

内皮细胞特异性因子ESM-1在肝癌血管内皮细胞的表达及作用

目的本研究拟通过分离纯化肝癌的血管内皮细胞，检测内皮细胞特异性分子1（ESM-1）在肝癌内皮细胞中的表达，并探讨其变化与肿瘤血管生成和侵袭的关系。方法收集山东大学附属省立医院肝胆外科行手术切除治疗且经术后病理证实的新鲜肝癌组织和癌旁组织。应用CD31单抗标记的免疫磁珠法进行分离并纯化血管内皮细胞，经内皮细胞鉴定并分析细胞纯度，应用荧光实时定量PCR、Westernblot等方法检测血管内皮细胞中ESM-1的表达。应用酶联接免疫吸附剂测定（ELISA）法检测相应肝癌患者及正常对照者血清中ESM-1的水平。结果经测定，ESM-1在肝癌患者血清中为（12．643±2．280）ng／mL，相比正常对照（4．660±1．172）ng／mL表达水平明显升高（t=10．16，P〈0．01），同时，在肝癌内皮细胞中ESM-1的mRNA和蛋白水平的表达均明显升高。结论ESM．1可能参与了肝癌的血管生成和侵袭过程，有望作为新的肿瘤治疗靶点。     

Effect of VEGF,P53 and telomerase on angiogenesis of gastric carcinoma tissue

Objective:To investigate the effect of vascular endothelial growth factor(VEGF),P53 and telomerase on angiogenesis in gastric carcinoma tissue.Methods:A total of 95 surgical resection samples of gastric cancer tissue after pathological diagnosis are collected to observe the VEGF,P53 and telomerase expression using immunohistochemical methods.Relationship between their expression and its influence on angiogenesis in gastric carcinoma tissue were analyzed.Results:Microvascular density(MVD)and the expression of VEGF,P53 and telomerase were positively correlated.Expression of VEGF and P53 protein were related to tumor type and lymph metastasis,and also a correlation was observed between P53 and VEGF.The telomerase expression had no correlation with VEGF,and P53.Conclusions:VEGF angiogenesis has a angiogenesis promoting effect on gastric cancer tissue development and plays an important role in tumor generation and metastasis.Mutant P53 promotes the tumor angiogenesis generation by adjusting VEGF.Telomerase has a certain role in promoting activity of angiogenesis through different way rather than P53.     

大肠癌CD24的表达及其与肿瘤细胞增殖和血管形成的关系

目的:探讨CD24在大肠癌中的表达及其与细胞增殖、血管生成的关系.方法:运用流式细胞术直接免疫荧光法检测66例大肠癌肿瘤组织及相应正常大肠黏膜CD24的表达量.CD24蛋白表达量以阳性率(PPC)和平均荧光强度MFI值表示.运用免疫组织化学法检测肿瘤组织CD34,PCNA的表达情况,根据CD34的染色情况计算出大肠癌组织的微血管密度(microvessel density),根据PCNA染色情况计算出肿瘤细PCNA标记指数.结果:大肠癌肿瘤组织CD24阳性率90.40%(75.10%-96.35%)明显高于相应的癌旁组织36.15%(32.00%-53.28%)(χ2=6.877,P＜0.001).大肠癌肿瘤组织CD24蛋白MFI值18.10(11.45-25.43),明显高于正常黏膜组织8.41(5.59-10.33)(χ2=6.934,P＜0.001).浸润型、高Dukes分期、高pTNM分期及有淋巴结转移的癌组织中CD24蛋白的平均荧光强度显著高于对应组(P＜0.05).浸润型、低分化、高Dukes分期、高pTNM分期及有淋巴结转移的癌组织中CD24蛋白阳性百分率显著高于对应组(P＜0.05).在CD24阳性表达病例中,PCNA的表达随着CD24表达强度的升高而升高(P＜0.05).大肠腺癌肿瘤细胞CD24阳性表达率与MVD呈正相关(r=0.243,P=0.050).而CD24蛋白平均荧光强度与MVD未见明显相关(r=0.115,P=0.358).结论:CD24在大肠腺癌中表达水平明显上调,并与肿瘤细胞增殖、血管生成密切相关.     

一氧化氮合酶和微血管生成与胃癌发展的关系

目的　研究诱导型一氧化氮合酶 (iNOS)在人胃癌组织中的表达及其与胃癌微血管形成、淋巴结转移及临床分期的关系。方法　采用免疫组化S P法检测 50例原发性胃癌组织、癌周组织及 2 0例正常胃黏膜组织中iNOS的表达 ,同时检测微血管密度 (MVD) ,以抗CD3 4标记血管内皮细胞 ,并分析其与肿瘤行为之间的关系。结果　 50例胃癌组织中iNOS阳性表达率为 70 .0 % ,MVD均值为 2 2 .0± 9 .8,显著高于癌周组织 (16.2 % ,6.1± 3 .4)和正常胃组织 (15.0 % ,5.5± 2 .6;P <0 .0 1)。按TNM分期 ,Ⅳ期胃癌组织iNOS阳性表达率为 93 .8% ,MVD为 42 .3± 3 .7,两者显著高于Ⅰ、Ⅱ、Ⅲ期 ,差异有显著性 (P <0 .0 1)。有淋巴结转移组iNOS的阳性表达率为 84.6% ,MVD均值为 2 7.4± 6.5;无淋巴结转移组iNOS阳性表达率为 54.2 % ,MVD均值为 15.3± 4.7,两组差异有显著性 (P <0 .0 5)。iNOS阳性表达组及高MVD值 (≥ 2 2 .0 )组的 3年生存率均显著低于iNOS阴性表达组及低MVD值 (<2 2 .0 )组 ,差异有显著性 (P <0 .0 5)。结论　胃癌组织中iNOS高阳性表达 ,随着iNOS阳性表达的增强 ,MVD值也增加 ,两者呈正相关。iNOS的表达及MVD与胃癌TNM分期、淋巴结转移及预后有密切关系。iNOS的表达及MVD值可作为判断胃癌预后的重要指标     

Expression of insulin-like growth factor binding protein-2 in gastric carcinoma and its relationship with cell proliferation

INTRODUCTION The insulin-like growth factor (IGF) system plays a crucial role in normal cell proliferation and malignant transformation[1,2]. It comprises IGF-Ⅰand IGF-Ⅱ, the typeⅠand Ⅱ receptors[3], and a family of IGF binding proteins (IGFBPs) that …     

贲门癌组织环氧化酶-2和血管生成因子的表达及其与血管生成的关系

目的:探讨环氧化酶-2(COX-2)和血管生成因子(VEGF)在贲门癌组织中的表达及其与肿瘤血管生成的关系.方法:免疫组化法检测贲门癌手术切除标本46例和癌旁正常黏膜标本21例中COX-2,VEGF表达.采用抗CD34抗体标记微血管内皮细胞,计算微血管密度(MVD).分析COX-2,VEGF表达与MVD和贲门癌主要临床病理特征的相关性.结果:贲门癌组织COX-2,VEGF阳性表达率、MVD值显著高于癌旁正常黏膜的(80.4% vs 14.3%,x~2=26.22,P<0.01;76.1% vs 19.1%,x~2=19.28,P<0.01:31.95±3.87 vs 16.28±1.55,t=17.76,P<0.01).COX-2,VEGF表达、MVD值与肿瘤临床TNM分期和淋巴结转移密切相关,TNM分期中Ⅲ Ⅳ期的贲门癌组织中COX-2,VEGF表达率、MVD值显著高于Ⅰ Ⅱ期的(90.3% vs 60.0%,x~2=5.91,P<0.05;96.8% vs 46.7%,x~2=16.13,P<0.01;33.43±3.34 vs 28.90±3.08,t=4.42,P<0.01).伴有淋巴结转移的贲门癌组织中COX-2,VEGF表达率,MVD值显著高于无淋巴结转移的(94.1% vs 41.7%,x~2=15.51,P<0.01:91.2% vs 50.0%,x~2=9.56,P<0.01;33.53±3.21 vs 27.48±1.03,t=6.38,P<0.01).Spearman等级相关分析表明,COX-2,VEGF表达与MVD呈显著正相关(r= 0.823:r=0.892,P<0.01).结论:COX-2,VEGF异常表达及其诱导的血管生成在贲门癌的侵袭和淋巴结转移中起重要作用.     

Preliminary study correlating CX3CL1/CX3CR1 expression with gastric carcinoma and gastric carcinoma perineural invasion

AIM:To study the relationship between the CX3CL1chemokine,its receptor CX3CR1,and gastric carcinoma/gastric carcinoma perineural invasion(PNI).METHODS:Thirty cases of gastric carcinoma were surgically resected(radical resection or palliative resection)between February 2012 and July 2012.Tumour and tumour-adjacent tissues were evaluated for the presence of CX3CL1(ELISA)and CX3CR1(immunohistochemistry and Western blotting)in an effort to analyse the relationship between CX3CL1/CX3CR1 and gastric carcinoma/gastric carcinoma PNI.RESULTS:Of these 30 cases,14 were PNI-positive(46.7%).No significant differences in CX3CL and CX3CR1 expression in tumour-adjacent tissues were found between the PNI positive and negative groups.Expression levels of CX3CL and CX3CR1 in tumour tissues were significantly higher than those in adjacent tissues(P<0.01),and were significantly higher in tumour tissues from the PNI-positive group compared to the PNI-negative group(P<0.01).CONCLUSION:CX3CL1/CX3CR1 expression may be associated with the occurrence and development of gastric carcinoma as well as gastric carcinoma PNI.     

血管内皮生长因子165基因对人胃癌细胞在体外生长及其受体表达的影响

目的:将已构建的重组腺病毒Ad-VEGF165进行扩增和纯化并观察其对人胃腺癌细胞(BGC-823)在体外生长及其受体表达的影响.方法:以人胚肾293细胞对重组腺病毒Ad-VEGF165和对照病毒Ad-GFP进行包装、扩增后感染BGC-823N胞,应用MTT比色法分析VEGF165对该种细胞体外生长的影响,并以免疫细胞化学方法检测该种细胞VEGFR-2的表达情况.结果:成功扩增及纯化了重组腺病毒Ad-VEGF165及对照病毒Ad-GFP,获得约3.2×1013pfu/L滴度的重组腺病毒和2.0×1013 pfu/L滴度的对照病毒.当感染复数(MOI)为20时转导率即接近100%而无明显细胞中毒现象.MTT结果显示Ad-VEGF165组吸光度明显高于Ad-GFP组(24 h:0.960±0.0 1 vs 0.737±O.01,P＜0.01:48 h:1.321±0.03 vs0.981±0.02,P＜0.01:72 h:1.663±0.03 vs 1.207±0.01,P＜0.01)及对照组(24 h:0.960±0.01 vs 0.724±0.03.P＜0.01:48 h:1.321±0.03 vs 0.968±0.01.P＜0.01:72 h:1.663±0.03 vs 1.185±0.02,P＜0.01).另外,在该细胞株上检测到了VEGFR-2的表达,且在Ad-VEGF165组其表达明显高于Ad-GFP组(62.5%vs37.6%,P＜0.01)和对照组(62.5%vs 34.1%,P＜0.01).结论:VEGF对胃癌细胞有直接的促生长作用,并可上调其主要受体VEGFR-2的表达水平,从而进一步证实了VEGF对胃癌细胞的自分泌作用.     

Expression of NOS and HIF-1α in human colorectal carcinoma and implication in tumor angiogenesis

AIM: To study CD34, CD105, inducible nitric oxide synthase (iNOS), endogenous nitric oxide synthase (eNOS), and hypoxia-inducible factor 1 (HIF-1) alpha expression in human colorectal carcinomas. METHODS: The tissue microarrays (TMAs) were made up of 80 cases of colorectal carcinoma and 80 cases of non-neoplasm colorectal mucosa. The expression of CD34, CD105, NOS and HIF-1alpha was detected by immunohistochemistry (S-P). RESULTS: iNOS and HIF-1alpha expression in colorectal carcinoma was significantly higher than in non-neoplasm colorectal mucosa (c2 = 43.166, P < 0.01; c2 = 10.4278, P < 0.01); eNOS expression in colorectal carcinoma was significantly lower than in non-neoplasm colorectal mucosa (c2 = 11.354, P < 0.01). The expression of iNOS correlated with differentiation (c2 = 18.141, P < 0.01), invasive depth (c2 = 4.748, P < 0.01), and Micro vessel density (MVD) (t = 2.327, P < 0.05). The expression of HIF-1alpha was correlated with infiltrating depth (c2 = 4.397, P < 0.05), Dukeos staging (c2 = 4.255, P < 0.05), and MVD (t = 2.272, P < 0.05). No correlation was found in eNOS expression. CONCLUSION: Over-expression of iNOS and HIF-1alpha in colorectal carcinoma is correlated with the biological character MVD.     

5-脂氧合酶mRNA在食管鳞癌中的表达及与血管生成的关系

目的探讨5-脂氧合酶（5-LOX）和微血管密度（MVD）在食管鳞状上皮细胞癌（ESCC）组织中的表达及相关关系，及5-LOX与肿瘤浸润和转移的关系。方法用半定量RT-PCR法测定35例ESCC患者癌组织（T）和相邻癌旁组织（N）中5-LOX mRNA的表达，求得T／N值。同时用免疫组织化学法测定癌组织和癌旁正常组织中微血管密度（MVD）的T／N值。结果在35例ESCC患者中，33例5-LOX mRNA的T／N值〉1．0，占94．3％，34例MVD的T／N值〉1．0，占97．1％。5-LOX mRNA和MVD与食管鳞癌的肿瘤大小、浸润深度和淋巴结转移、肿瘤分化程度有关。5-LOX mRNA的T／N值与MVD的T／N值呈正相关。结论5-LOX与食管鳞癌血管生成和肿瘤浸润转移密切相关，其高表达可能促进肿瘤血管生成，从而促进ESCC的浸润和转移。